Current challenges to underpinning the genetic basis for cholangiocarcinoma

Introduction: Cholangiocarcinoma (CCA) is an aggressive cancer type with a dismal prognosis. CCA typically presents at an advanced stage when surgical resection is not feasible, and systemic chemotherapy is generally of limited benefit. Thus, developing effective therapies against this deadly tumor is imperative and remains an unmet need. The advent of high-throughput approaches has led to a better delineation of each CCA subtype’s molecular landscape and the identification of promising candidates for targeted therapies. In this scenario, the recent approval of pemigatinib, a pan-Fibroblast Growth Factor Receptor (FGFR) inhibitor, for the treatment of the CCA subtype characterized by FGFR2 mutations, represents the first of numerous novel therapies against this disease. Areas covered: This review provides an overview regarding the current scenario and knowledge of the CCA genomic landscape and the potentially actionable molecular aberrations in each CCA subtype. Expert opinion: The establishment and advances of high-throughput methodologies applied to genetic and epigenetic profiling are changing many cancer types' therapeutic landscape, including CCA.The large body of data generated must be interpreted appropriately and eventually implemented in clinical practice. The following advancements toward precision medicine in CCA management will require designing better clinical trials with improved methods to stratify biliary tumor patients.